HIV from subtype B heterosexuals have longer V1-V2 loops than HIV from subtype B homosexuals

PANDO MA; NADAI Y; EYZAGUIRRE LM; CLEGHORN F; BLATTNER WA; JACK N; AVILA MM; CARR JK

Mexico

Conferencia; XVII International AIDS Conference; 2008

IAS

Background: Sexual transmission accounts for the majority of HIV infections worldwide but the viral properties that determine transmission fitness have not been elucidated. Studies have suggested that changes in the V1-V2 domain of the envelope glycoprotein can affect receptor/correceptor utilization and infection efficiency. Changes in the lengths and/ or glycosylation patterns of the V1-V2 loops may affect cell entry by influencing the accessibility of the viral envelope receptor-binding domain. The objective was to compare the length and the number of N-linked glycosylation sites (NLGS) in the env region of HIV sequences from seroconverters from a Trinidad cohort (subtype B, heterosexual transmission) to those from Argentinian cohorts (subtype B, homosexual transmission).Sexual transmission accounts for the majority of HIV infections worldwide but the viral properties that determine transmission fitness have not been elucidated. Studies have suggested that changes in the V1-V2 domain of the envelope glycoprotein can affect receptor/correceptor utilization and infection efficiency. Changes in the lengths and/ or glycosylation patterns of the V1-V2 loops may affect cell entry by influencing the accessibility of the viral envelope receptor-binding domain. The objective was to compare the length and the number of N-linked glycosylation sites (NLGS) in the env region of HIV sequences from seroconverters from a Trinidad cohort (subtype B, heterosexual transmission) to those from Argentinian cohorts (subtype B, homosexual transmission). Methods: The samples analyzed in this study were collected during different incidence studies, two in Argentina and one in Trinidad and Tobago. All samples were collected within 4 months of seroconversion. Samples of peripheral blood mononuclear cells were used for DNA extraction. A 3.3kb section of the HIV genome (5884-9157 on HXB2) including the entire envelope gene was amplified using a nested PCR strategy. The amplified products were then sequenced using an Applied Biosystems 3130xl DNA capillary sequencer.The samples analyzed in this study were collected during different incidence studies, two in Argentina and one in Trinidad and Tobago. All samples were collected within 4 months of seroconversion. Samples of peripheral blood mononuclear cells were used for DNA extraction. A 3.3kb section of the HIV genome (5884-9157 on HXB2) including the entire envelope gene was amplified using a nested PCR strategy. The amplified products were then sequenced using an Applied Biosystems 3130xl DNA capillary sequencer. Results: Twenty-eight samples from Argentina and 33 from Trinidad were analyzed. Trinidad seroconverters have longer V1-V2 loops than Argentinean seroconverters (72.94 vs 68.68 amino acids, p<0.005) or prevalent cases elsewhere (72.50 vs. 69.63, p<0.005).There were also more NLGS in Trinidad samples than Argentinian samples (5.82 vs. 5.54) or prevalent cases elsewhere (5.82 vs. 5.68), but this result did not reach statistical significance.Twenty-eight samples from Argentina and 33 from Trinidad were analyzed. Trinidad seroconverters have longer V1-V2 loops than Argentinean seroconverters (72.94 vs 68.68 amino acids, p<0.005) or prevalent cases elsewhere (72.50 vs. 69.63, p<0.005).There were also more NLGS in Trinidad samples than Argentinian samples (5.82 vs. 5.54) or prevalent cases elsewhere (5.82 vs. 5.68), but this result did not reach statistical significance. Conclusions: Envelope sequence analysis of incident HIV infections showed that subtype B from heterosexual transmissions (Trinidad) had longer V1-V2 loops than those from homosexual transmissions (Argentina). The length of V1- V2 has an impact on neutraliziation sensitivity and affinity for DC-SIGN, among other things, and may be related to transmission efficacy in heterosexualsEnvelope sequence analysis of incident HIV infections showed that subtype B from heterosexual transmissions (Trinidad) had longer V1-V2 loops than those from homosexual transmissions (Argentina). The length of V1- V2 has an impact on neutraliziation sensitivity and affinity for DC-SIGN, among other things, and may be related to transmission efficacy in heterosexuals